Analysis of a new therapeutic target and construction of a prognostic model for breast cancer based on ferroptosis genes

Qi Li; Hengchen Liu; Yun Jin; Yuanquan Yu; Yihang Wang; Di Wu; Yinghao Guo; Longfu Xi; Dan Ye; Yanzhi Pan; Xiaoxiao Zhang; Jiangtao Li

doi:10.1016/j.compbiomed.2023.107370

Analysis of a new therapeutic target and construction of a prognostic model for breast cancer based on ferroptosis genes

Comput Biol Med. 2023 Oct:165:107370. doi: 10.1016/j.compbiomed.2023.107370. Epub 2023 Aug 24.

Authors

Qi Li¹, Hengchen Liu², Yun Jin³, Yuanquan Yu⁴, Yihang Wang⁵, Di Wu⁶, Yinghao Guo⁷, Longfu Xi⁸, Dan Ye⁹, Yanzhi Pan¹⁰, Xiaoxiao Zhang¹¹, Jiangtao Li¹²

Affiliations

¹ Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China; Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China. Electronic address: zyeylq@zju.edu.cn.
² Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, Zhejiang Provincial Clinical Research Center for Cancer, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China. Electronic address: 2322043@zju.edu.cn.
³ Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China; Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China. Electronic address: jinyunzeyy@zju.edu.cn.
⁴ Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China; Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China. Electronic address: zjuyyq@zju.edu.cn.
⁵ Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China; Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China. Electronic address: 18888922251@163.com.
⁶ Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China; Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China. Electronic address: 0621228@zju.edu.cn.
⁷ Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China; Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China. Electronic address: guoyinghao07@zju.edu.cn.
⁸ Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China; Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China. Electronic address: 12018464@zju.edu.cn.
⁹ Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China; Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China. Electronic address: 2316030@zju.edu.cn.
¹⁰ Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China; Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China. Electronic address: 2267765835@qq.com.
¹¹ Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China; Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China. Electronic address: zxiaoxiao204@163.com.
¹² Department of Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China; Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China. Electronic address: zrljt@zju.edu.cn.

PMID: 37643511
DOI: 10.1016/j.compbiomed.2023.107370

Abstract

Breast cancer, which is the most common malignant tumor among women worldwide and an important cause of death in women. The existing prognostic model for patients with breast cancer is not accurate as breast cancer is resistant to commonly used antitumor drugs. Ferroptosis is a novel mechanism of programmed cell death that depends on iron accumulation and lipid peroxidation. Various studies have confirmed the role of ferroptosis in tumor regulation and ferroptosis is now considered to play an important role in breast cancer development. At present, the association between breast cancer prognosis and ferroptosis-related gene expression remains unclear. Further exploration of this research area may optimize the evaluation and prediction of prognosis of patients with breast cancer and finding of new therapeutic targets. In this study, clinical factors and the expression of multiple genes were evaluated in breast cancer samples from the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database database. Eleven prognostication-related genes (TP63, IFNG, MT3, ANO6, FLT3, PTGS2, SLC1A4, JUN, SLC7A5, CHAC1, and TF) were identified from differentially expressed genes to construct a survival prediction model, which showed a good prediction ability. KEGG pathway analysis revealed that immune-related pathways were the primary pathways. ssGSEA analysis showed significant differences in the distribution of certain immune-related cell subsets, such as CD8⁺T cells and B cells, and in the expression of multiple immune genes, including type II IFN response and APC coinhibition. In addition, 10 immune targets related to ferroptosis in breast cancer were found: CD276, CD80, HHLA2, LILRA2, NCR3LG1, NECTIN3, PVR, SLAMF9,TNFSF4, and BTN1A1. Using TCGA, new ferroptosis genes related to breast cancer prognosis were identified, a new reliable and accurate prognosis model was developed, and 10 new potential therapeutic targets different from the traditional targeted drugs were identified to provide a reference for improving the poor prognosis of patients with breast cancer.

Keywords: Breast cancer; Ferroptosis; Immunotherapy targets; Prognostic model.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis
B7 Antigens
Breast
Breast Neoplasms* / drug therapy
Breast Neoplasms* / genetics
Female
Ferroptosis* / genetics
Humans
Immunoglobulins
OX40 Ligand
Prognosis

Substances

TNFSF4 protein, human
OX40 Ligand
HHLA2 protein, human
Immunoglobulins
CD276 protein, human
B7 Antigens